Acute myocardial infarction (“AMI”) is the leading cause of death in the United States and industrialized countries. Research conducted for over the past 15 years has demonstrated that several types of minimally or modestly stenotic atherosclerotic plaques, termed vulnerable plaques, are precursors to coronary thrombosis, myocardial ischemia, and sudden cardiac death. Postmortem studies have identified one type of vulnerable plaque, i.e., the thin-cap fibroatheroma (“TCFA”), as the culprit lesion in approximately 80% of sudden cardiac deaths. Over 90% of TCFA's are found within the most proximal 5.0 cm segment of each of the main coronary arteries (left anterior descending—LAD; left circumflex—LCx; and right coronary artery—RCA). The TCFA is typically a minimally occlusive plaque characterized histologically by the following features: a) thin fibrous cap (<65 μm), b) large lipid pool, and c) activated macrophages near the fibrous cap. It is hypothesized that these features predispose TCFAs to rupture in response to biomechanical stresses. Following the rupture, the release of procoagulant factors, such as tissue factor, create a nidus for thrombus formation and the potential for an acute coronary event. While TCFAs are associated with the majority of AMIs, recent autopsy studies have shown that coronary plaques with erosions or superficial calcified nodules may also precipitate thrombosis and sudden occlusion of a coronary artery.
Although autopsy studies have been valuable in determining features of culprit plaques, the retrospective nature of these studies may limit their ability to quantify the risk of an individual plaque for causing acute coronary thrombosis. For instance, TCFAs are a frequent autopsy finding in asymptomatic or stable patients, and are found with equal frequency in culprit and non-culprit arteries in acute coronary syndromes. Moreover, disrupted TCFAs have been found in about 10% of non-cardiac deaths. Recent findings of multiple ruptured plaques and increased systemic inflammation in acute patients have challenged the notion of a single vulnerable plaque as the precursor for AMI. A better understanding of the natural history and clinical significance of these lesions may accelerate progress in the diagnosis, treatment and prevention of coronary artery disease.
An exemplary approach to studying the evolution of vulnerable plaques is a non-invasive or intracoronary imaging of individual lesions at multiple points in time. Unfortunately, the microscopic features that characterize vulnerable plaque are not reliably identified by the conventional imaging technologies, such as intravascular ultrasound (“IVUS”), catscan (“CT”), and magnetic resonance imaging (“MRI”). While experimental intracoronary imaging modalities such integrated backscatter IVUS, elastography, angioscopy, near-infrared spectroscopy, Raman spectroscopy and thermography have been investigated for the detection of vulnerable plaque, it is believed that no method other than optical coherence tomography (“OCT”) has been shown to reliably identify the characteristic features of these lesions.
OCT is an optical analog of ultrasound that provides high-resolution (˜10 μm) cross-sectional images of human tissue. OCT has been established as an accurate method for characterizing the microscopic features associated with vulnerable plaque. This technology can also be used to quantify macrophage content within atherosclerotic plaque. Intracoronary optical imaging using such technology is safe, and images obtained from patients have features substantially identical to those identified ex vivo. Thus, OCT has the ability to provide a large amount of information about plaque microstructure. This technology may play an important role in improving the understanding of vulnerable coronary plaques in patients.
Strong attenuation of light in blood may present a significant challenge for intravascular optical imaging methods. To overcome this potential obstacle, intermittent 10 cc flushes of saline through a guiding catheter can provide an average of 2 seconds of clear viewing during which effective images can be captured, as is shown in FIG. 1B. For example, FIG. 1B illustrates an analysis of the time of angiographic lumen attenuation following a 6 cc contrast injection at three separate locations, shown in part A of FIG. 1B. As can be seen from part B of FIG. 1B, the angiographic lumen attenuation following the 6 cc contrast injection at a rate of 3 cc/s demonstrates a complete filling for the duration of the purge (approximately 2 seconds) regardless of the location. Additionally, saline flushing of a blood vessel for a limited duration (for example, less than 30 seconds) is safe, and generally does not result in a myocardial ischemia. This approach can provide exceptional cross-sectionally images of coronary vasculature. However, the combination of the limited flush duration and low image acquisition rate may reduce comprehensive coronary screening.
One proposed solution has been to change the optical properties of blood. The primary mechanism of optical attenuation in blood is optical scattering. For instance, matching the refractive index of the red blood cells, white blood cells and platelets with that of a serum decreases optical scattering. This approach has resulted in a 1.5-fold increase in penetration of OCT when diluting blood with Dextran. Unfortunately, since the optical attenuation of blood is so high, at least a 10-fold improvement would be preferable to allow for effective intracoronary OCT imaging in patients.
Another proposed solution is to completely occlude the artery, and replace blood with saline. This technique that is commonly deployed in angioscopic imaging requires proximal balloon occlusion. Following vascular occlusion, all of the remaining blood in the vessel is replaced with saline. This conventional method allows a cross-sectional optical imaging of the entire coronary tree. While this procedure is commonly conducted in Japan, the potential for coronary dissection and myocardial ischemia precludes widespread clinical application of this procedure.
Still another proposed solution is to purge the blood vessel with optically transparent blood substitutes. Blood substitutes that are transparent in the infrared can potentially provide clear imaging for an extended duration. This method has achieved significantly improved imaging in murine myocardium by replacing blood with Oxyglobin. Although these compounds may hold promise for future clinical application, they are not yet approved for human use.
A further proposed solution is to increase the frame rate of OCT scans. Since the goal is to acquire a sufficient number of images to comprehensively screen coronary arteries, a straightforward approach would be to accept the clear viewing time provided by conventional saline flushing, and increase the frame rate of OCT scans dramatically. Two possibilities exist for increasing the frame rate of OCT scans: a reduction of the number of A-lines per image, and an increase of the radial scan rate.
Similarly to many imaging methods, OCT images are acquired in a point sampling fashion and are composed of multiple radial scans or A-lines. To increase the image rate, it is possible to reduce the number of A-lines per image by increasing the catheter rotation rate. Image quality degrades rapidly in such case, however, manifested by a decrease in transverse resolution as can be seen in FIG. 1A. For example, image A of FIG. 1A depicts a sample image generated using OCT imaging at a rate of 4 frames per second having 500 A-line scans per frame. Image B of FIG. 1A depicts a sample image generated using OCT imaging at a rate of 40 frames per second having 50 A-line scans per frame. As can be clearly seen, the image quality of Image A far exceeds the image quality of Image B. This degradation is unacceptable for most clinical applications.
A second possibility is to increase the radial scan rate. For technical reasons specific to the current OCT paradigm, an increase in A-line rate may result in an unacceptable penalty in signal to noise ratio, and thus, images of sufficient quality for accurate diagnosis cannot be obtained.
Therefore, there is a need to provide a method and apparatus that combine quality imaging of internal surfaces of blood vessels and other biological structures and effective imaging of segments of the internal surfaces of the blood vessels.